The full texts of the two papers (both by Manson et al.) — one on the use of vitamin D supplements and the other on the use of marine n-3 fatty acids — are available on line, so interested readers can read the papers for themselves. They suggest that the benefits of vitamin D3 and marine n-3 fatty acids (also known as omega-3 fatty acids) are limited in the prevention of both cardiovascular diseases and cancer.

It has to be pointed out up front that the two papers had significant strengths as well as significant weaknesses. In the “strengths” column:

It would be impossible to go into all the details of these two studies in this brief commentary. Suffice it to say that the conclusions reached by the research team are as follows:

Daily supplementation with high-dose vitamin D3 for 5 years among initially healthy adults in the US (compared to a placebo) did not reduce the overall incidence of either invasive cancer of any type or major cardiovascular events (a composite of myocardial infarction, stroke, or death from cardiovascular causes).

Daily supplementation with n-3 fatty acids for 5 years among initially healthy adults in the US (compared to a placebo) also did not reduce the overall incidence of either invasive cancer of any type or major cardiovascular events.

There was a small difference in the number of men who were diagnosed with prostate cancer among men taking the vitamin D3 supplements (192/12,927 or 1.49 percent) compared to the placebo (219/12,944 or or 1.69 percent), with a hazard ratio = 0.88. However, this difference was not statistically significant.

There was also no statistically significant difference in the number of men actually dying of prostate cancer over the course of the trial.

However, compared to the patients on the placebos:

There is some evidence that the overall numbers of patients who were dying of cancer started to decrease after the first 2 years of being on vitamin D3.

There is no evidence that the overall numbers of patients being diagnosed with cancer started to decrease after the first 2 years of being on the n-3 fatty acids.

There seem to have been no significant differences in the incidence of adverse events among the men taking vitamin D3 or the n-3 fatty acids or both

So … perhaps we can acknowledge that for those who want to take supplements like vitamin D3 and n-3 fatty acids on a regular basis as they get older, there may be a cancer protective effect over time, with minimal risk for side effects of such treatment, but just how much the benefit might be over time is still unclear. It would probably take a 20-year-long trial to clarify this.

There is no suggestion that the patients in the VITAL study are going to be followed for another 15 years (which is probably a great pity, but is also a financial reality; this sort of long-term follow-up is very expensive to carry out).

The trial is obviously a fraud bent to work against low-cost supplements. 2000 IU of Vitamin D3 is a joke. Minimum supplementation of Vitamin D3 for cancer treatment or prevention needs to be in the 4,000 to 10,000 IU range. Minimum.

“There is some evidence that the overall numbers of patients who were dying of cancer started to decrease after the first 2 years of being on vitamin D3.”

This is correct, but I would caution that the cancer deaths in the 5 years of follow-up were almost certainly never due to prostate cancer (anyone who had cancer detected at initiation was screened out).

“There is also some evidence that the overall numbers of patients being diagnosed with cancer started to decrease after the first 2 years of being on the n-3 fatty acids.”

I see the opposite effect on Table 2 from what you state. The hazard ratio (with 95% confidence interval) is 1.13 (1.00-1.28). This means that those taking omega-3 pills had a 13% greater incidence of any cancer after 2 years.

I would also caution readers, many of whom have already been diagnosed with advanced or recurrent prostate cancer, that this trial had to do with prevention of incidence rather than prevention of recurrence. The safety of Vitamin D supplementation in men who have already been confirmed to have prostate cancer has not been established. Observational studies have suggested that omega-3s and very high doses of vitamin D have been associated with higher grade prostate cancer. For example:

You are correct. This is what happens when you “cut and paste” things but then fail to modify the material that you have cut and pasted because you got distracted by your wife asking you to get the dogs in from the yard! I have made an appropriate adjustment.

As Allen has noted above, and whether you want to believe it or not, one of the problems with high-dose vitamin D3 supplementation is that it has been strongly associated with a high risk for induction of more aggressive forms of prostate cancer. In other words, it may well prevent the lower-risk forms of prostate cancer that are unlikely to ever kill you in the first place but increase the risk of aggressive, clinically significant prostate cancer. I’m not at all sure that I would want to place the bet that Walt appears to be suggesting.

I would also point out that the VIDA trial gave participants a huge initial dose of 200,000 IU at the start of the first month and 100,000 IU once a month thereafter and found exactly the same thing — no effect on incidence of any kind of cancer. Don’t forget that Vitamin D is stored in liver and fat.

Also, the researchers in the VITAL trial looked at people who had higher blood levels of Vitamin D at baseline, and found there was no effect on cancer incidence in them either.

Serum Vitamin D is a well-regulated biochemical process, as are all steroid hormones. When one takes in a lot of vitamin D, the level of vitamin D binding protein is upregulated and vitamin D receptors are downregulated, making less of it bioavailable. One can overload the system, but that creates toxicity. Also, we have mechanisms to interconvert most steroids, and high levels of vitamin D have been associated with increased testosterone levels — not a desirable outcome while on ADT.

The reason we do large, randomized, clinical trials like VITAL is because the observational studies like your link are prone to error. It’s time to let go of them. One of the findings was that the lack of effect was equal among African-Americans.

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